| Project/Area Number |
12670679
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Nagasaki University |
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Principal Investigator |
ASHIZAWA Naoto Nagasaki University, The Third Department of Internal Medicine, Lecturer, 医学部・附属病院, 講師 (10301368)
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| Co-Investigator(Kenkyū-buntansha) |
TSUKAZAKI Tomoo Department of Oral Pathology, Nagasaki University School of Dentistry, Associate Professor, 歯学部, 助教授 (50315230)
YANO Katsusuke Nagasaki University School of Medicine, The Third Department of Internal Medicine, Professor, 医学部, 教授 (50039864)
SETO Shinji Nagasaki University School of Medicine, The Third Department of Internal Medicine, Associate Professor, 医学部, 助教授 (00136657)
YAMASHITA Shunichi Nagasaki University School of Medicine, Department of Molecular Medicine, Atomic Bomb Disease Institute, Professor, 医学部, 教授 (30200679)
NAGASAKI Ohtsuru University School of Medicine, Department of Molecular Medicine, Atomic Bomb Disease Institute, Assistant Professor, 医学部, 助手 (00233198)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Keywords | Cardiac Fibrosis / Cardiac Hypertrophy / TGF-β / Norepinephrine / MAPK / Smad / Ca antagonist / Signal Transduction / Norepinephrine / 心線維芽細胞 / Smad系 / MAPK系 |
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| Research Abstract |
Cardiac fibrosis results from proliferation of interstitial fibroblasts and concomitant increased biosynthesis of extracellular matrix (ECM) components, and is often complicated by cardiac hypertrophy. This study was conducted to investigate whether norepinephrine (NE) potentiates TGF-J3- induced cardiac fibrosis. In cultured neonatal rat cardiac fibroblasts, treatment with a combination of NE (10-5M) and TGF-β(1 ng/ml) increased cell proliferation and ECM protein (fibronectin, collagen I, III and PAI-1) expression. The 3TP-LUX activity was increased 2-3 fold when treated individually with NE or TGF-β, however, the 3TP-Lux activity increased by about 10 fold following treatment with a combination of NE and TGF-β. By using a dominant negative vector of the TGF-βtype II receptor, the synergistic effects were inhibited. The activin response element (ARE)-LUX activity in the presence of forkhead activin signal transducer-1 (FAST-1) increased by only 3 fold in cardiac fibroblasts. These data indicate that NE enhances cardiac fibrosis through TGF-β post-receptor signaling and MAPK is much more involved in TGF-β signaling in cardiac fibrosis than Smad.
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